Mutations

Mutations

A mutations are a change in the sequence of bases in DNA or RNA

Mutations are essential for evolution to occur

Mutations are the ultimate source of all new

genetic material within a species

Most have no effect at all

Some are beneficial

Some are harmful

Causes

Some happen spontaneously

Due to mistakes in DNA replication or in the

process of transcription

Others are caused by environmental factors

These factors are called mutagens

Germline mutations

Occur in gametes

Can be transmitted to offspring and will

be in every cell in the offspring

Causes

Somatic mutations

Occur in other cells of the body

Have little effect because these are

confined to one cell and its daughter cells

Can't be passed on to the offspring

Mutagens

Chromosomal Alterations

Changes in the structure of the chromosome(s)

Chromosomal Alterations

These tend to be very serious

Often result in the death of the organism in which they occur

If the organism survives it may be affected in multiple ways

Human example - Down Syndrome

A duplication mutation

3 #21 chromosomes

Point Mutations

Type Description Example Effect

Silent Mutated codon codes for the same amino acid

CAA (Glutamine)CAG Glutamine)

None

Missense Mutated codon coes for a different amino acid

CAA (Glutamine)CCA (Proline)

Variable

Nonsense Mutated codon is a premature stop codon

CAA (Glutamine)UAA (Stop)

Usually serious

Frameshift Mutations

A deletion or insertion of one or more nucleotides that changes the reading frame of the base sequence

Deletions take away nucleotides

Insertions add nucleotides

AUG-AAU-ACG-GUU = Start-Asp-Thre-Ala

AUG-AAA-UAC-GGU-U = Start - Lys-Tyr-Gly

Effects of Mutations

May be positive, negative, or neutral

Cells also have repair mechanisms to fix errors

If the damage is permanent it can't be fixed

Beneficial Mutations

Essential for evolution to occur

Increase chances of surviving or reproducing

Antibiotic resistance in bacteria

Town in Italy

protects from atherosclerosis

Harmful Mutations

Proteins that don't function properly

May cause genetic disorder or cancer

Genetic disorder

in one or a few genes

Cystic fibrosis

in a single gene

Cancer - uncontrolled cell growth

Some cancer genes can be inherited

Regulation of Gene Expression

Not all cells make or need the same proteins

Using a gene to make a protein is called gene expression

This needs to be regulated

When, Where and How much

We will look at regulation during transcription

Controlled by regulatory proteins

Bind to the DNA at places called regulatory

elements, which are near regions called

promoters

Regulation of Gene Expression

Regulatory proteins bind to these elements

Activators or Repressors

Interact with RNA polymerase which

transcribes DNA into mRNA

Activators promote transcription

Repressors prevent or inhibit transcription

Regulation of Initiation

Prokaryotic Gene Expression

It is much simpler

Regulation involves something called operons

A region of DNA that consists of one or more

genes that encode the proteins needed for

a specific function

The operator is the region of the operon

where regulatory proteins bind

http://www.youtube.com/watch?v=oBwtxdI1zvk

Eukaryotic Gene Expression

Very complicated

Many regulatory proteins and regulatory elements involved

Involved enhancers

Regions of DNA that can loop back and

interact with a gene's promoter

The TATA Box

Some patterns of regulatory elements are present in all genes

The TATA box is part of the promoter of most eukaryotic genes

Regulatory proteins bind here

When they are done binding RNA

polymerase recognized the complex and

goes to work transcribing the gene

Regulation during Development

Regulation is very important when an organism is developing

Genes need to be turned on and off in just

the right sequence and time

Homeobox genes are examples of genes that

regulate development

The switch on whole series of major

developmental genes

In insects the hox genes insure that

body parts develop in the right place.

Homeobox Genes

http://www.youtube.com/watch?v=LFG-aLidT8s

Gene Expression and Cancer

Mutations that cause cancer generally occur in two types of regulatory genes

Tumor-suppressor genes

Proto-Oncogenes

These genes produce regulatory proteins

that control the cell cycle

When these genes mutate - cells with

mutations divide rapidly and without limits

How Cancer Develops

Mutation inactivates Tumor suppressor

Cells proliferate

Mutation inactivates DNA repair gene

Mutation of proto-oncogene creates an oncogene

Mutation inactivates several more tumor suppressor genes

Cancer